The field of structural biology has developed dramatically over the last ten years, largely because of improvements in the techniques and applications of X-ray crystallography and multidimensional NMR spectroscopy. The three-dimensional structures and dynamics of macromolecules reveal mechanistic insights into protein function that cannot be gained in studies of whole cells, tissues or organisms. In turn, these insights provide molecular and cellular biologists with a rational framework for testing hypotheses about protein function. It is expected that the three-dimensional structures of proteins and their complexes will continue to have a substantial impact on our understanding of GI biology. Yet, the experimental determination of three-dimensional structures cannot keep pace with the rapid accumulation of novel gene sequences implicated in GI processes. Homology models derived from the known structures of related proteins will assist investigators in developing hypotheses that can be tested experimentally by mutagenesis and/or chemical modification of the protein and ligand. The major objective of the Protein Structure and Macromolecular Graphics (PSMG) Core is to provide DDRCC investigators with access to structural information specific to their research systems. This includes: 1) training and assistance in macromolecular modeling (homology modeling, mutational simulation, molecular docking) using continually updated graphics systems; 2) generation of structure images for slides, posters and publications; and 3) consultation and assistance with feasibility studies for protein structure determination by X-ray crystallography and/or NMR. The development of a central computing facility is a cost-effective means of utilizing the expensive software licenses and graphics workstations needed for this type of work. More importantly, it will provide investigators not principally engaged in protein structural analyses with training and guidance in molecular visualization and model building. Moreover, the PMSG facility will catalyze the structure determination process for new GI proteins by offering the resources and guidance needed for X-ray and NMR feasibility studies. The location of the facility within the Department of Biochemistry & Molecular Biophysics at the School of Medicine places it adjacent to laboratories principally focused on structural analysis of proteins and easily accessible to other users participating in the DDRCC.